Alpha-amino acids containing alpha, fluorinated-alkyl or cycloalkyl groups



Patented Dec. 15, 1953 UNITED STATES vALPHA-AMINO ACIDS CONTAINING-ALPHA, JFLUORIN-ATED-ALKYL TOR, CYCL'OALKYL .GROUPS -Joh1r' FrankIsontzand Maynard :Stanley Raasch, Wilmington} Del.,assignors to E. I.du Pont de -Nemours&" Company, Wilmington, Del.,-a cor- No'i'Drawing.ApplicationJune' 30, 1952, Serial No. 296,492

. 10 Claims.

This invention relates to fluorinewontaihing organic compounds "andjmoreparticularly, -to-a new class of fiuorosubstitutedamino acids.

Fluorosubstituted "aromatic aminocarboxylic acids have been 'knownheret'ofore. "Inthese acids such 'as the fluorophenylalanines andfluorotryptophane, the aromatic "nuclei are fluorosubstituted. However,no recoidedexam- .ple of either. a fluorosubstitutedaliphatic: or

cycloaliphatic. aminocarboxylic acid is known.

JAn objectoithe present invention is to provide a newclass offluorine-containing organic compounds. A further object is 'itoprovideanew class of iluorosubstituted aliphatic or cyclealiphaticaminocarboxylic a'cids. cific object is to provide new compoundsof valuein the important insecticide and'fungicidefield. Other objects will be"apparent from theidescription of the invention given hereinafter.

The above objects are" accomplished according to the. present inventionby' the prepara'tionpf aminocarboxylic acids wherein'ia carbon" alpha ito a carboxyl carries an amino group-arideither a "fiuorosubstitutedaliphatic or cy'cloaliphatic radical. Because of their ease ofsynthesis, reactivity, and biological activity, the preferred group ofthese compounds are the alpha-monoaminomonocarboxylic acids wherein thecarbon alpha to thecarboxyl carries affluorosubstitiited aliphatic orcycloaliphatic radical, particularly; those where the. alpha-amino.group-is, primary. Within the above preferredgroupofthese new compoundsare certain compounds that .are. outstanding because of their highphysiological activity, for instance, as curativefungicides 'and,

systemic aphicides. These are the fluorosubstituted, saturated straightchain aliphaticalpha- A more lspe- 2 the straight chain aliphaticradical attached to the carbon alpha to the carboxyl containing not morethan" 5 carbons, are'of "great value.

"The. fluorosubstituted amino acids "of thisinvention have thestructural" formula .T -RC'-O00H RFN Ra wherein R is :a.fiuorosubstituted .aliphaticJOr ,cycloaliphatic hydrocarbon radicalofjno more than 18 carbons and, preferably, no more 'tharf'l carbons;R1, is H, R, or an aliphaticor' cycloalipha-tic hydrocarbon radical of.no? more than 18 carbons. and, preferably no m'ore'than 7 carbons; andR2 and R3 which can be alike or'different, 'are H 'or aliphatic orcycloaliphatic hydrocarbon radicalsof no more than 18 carbons and,preferably, no more than 7 carbons each. :Because *of I theing-reater;physiological activity,

the preferred amino'acidszof this invention are those of the above typestructural formula wherein" R is a fluorosubstituted, particularly amonofluorosubstituted, saturated straight chain aliphatic hydrocarbonradical wherein the 'fluorine' substituents are on odd numbered carbonsand R1, R2, andRg are'all hydrogen. *Becauseof the readier availabilityofitheir intermediates the amino acids of the above type "bearing asaturated aliphatic hydrocarbonradical containing an odd numberofcarbonsybutno more than 5, l linearly arranged and possessing a*single terminal fluorine atom,are'especially preferred.

In. general, the" solubility ofthese compounds in aqueous solutions can"be increasedthrough salt formation involving either "theamino'prcarboxyl groups. When"Rz"andi'Rs"' are not hydrogen, zquaternarybetaine' salts may. be" formed. The activity of these compounds 'isnotliinited.

however, to the water-solubleforms sincethe copper salt of deltafluoronorvaline is also an eifective fungicide. These various salts arewell recognized in the organic" chemi'cal" art *as close chemicalequivalents to the free amino carboxylic acids and are consideredpartof-this'invention. The compounds of this invention can be ,pre-

. pared by type. reactions well known-in the art from a' wide selectionof 1 known -fluorosubstitu-ted intermediates. They can beopreparedbydirect :amination with-- ammonia or.- the requisite amine of thecorresponding alphachloro or bromocarboxylic acids. Alternately, theycan be prepared by the Bucherer et a1. hydantoin route or the Streckeraminonitrile method from the requisite aldehydes or ketones. The formerroute is preferred because of higher yields and greater reactionefiiciency. Further, the fluorosubstituted amino acids of this inventioncan be prepared by the condensation of the requisite fluorosubstitutedaliphatic or cycloaliphatic bromide or chloride with the sodioderivative of acetamidomalonic ester, phthalimidomalonic ester, oracetamidocyanoacetic ester and subsequent hydrolysis of the intermediateobtained. A still further route involves the condensation of therequisite fluorosubstituted aldehydes or ketones with hydantoin followedby reduction and hydroylsis.

The following examples in which all proportions are by weight unlessotherwise stated, illustrate the preparation and certain properties ofspecific compounds of this invention.

EXAMPLE I Part A.-Preparation of ethyl acetamido(Z-fluoroethyl) malonateTo a solution of 15.8 parts of sodium in about 550 parts of absoluteethyl alcohol was added 149 parts of ethyl acetamidomalonate and 87parts of l-bromo-2-fluoropropane (see Hofimann, J. Org. Chem. 15, 425(1950) and the resulting mixture was heated at the reflux for 15 hours.The white, solid precipitate of sodium bromide was removed from theresulting reaction mixture by filtration, the filtrate evaporated todryness, and the solid residue remaining washed with water. The crudeethyl acetamido(2-fluoroethyl)malonate thereby obtained wasrecrystallized from warm 2-B ethyl alcohol to give 62 parts in 3 cropsof white crystals, melting at 74-76" C.

AnaZ.-Calcd for CuHisNOsFZ F, 7.22%; N, 5.32% Found: F, 7.4%; N, 5.25%7.6%; 5.23

Part B.Preparation of DL-gamma-fluoro-alphaaminobutyrz'c acid A solutionof grams of the above ethyl acetamido-(2-fiuoroethyl)malonate in about60 parts of water containing about 7.5 parts of concentrated sulfuricacid was refluxed for hours. At the end of this time the sulfuric acidwas neutralized by adding an equivalent amount of barium hydroxide(about 24.5 parts) in the form of a hot aqueous solution. The resultingprecipitate of barium sulfate was removed by filtration and the aqueousfiltrate concentrated by evaporation under reduced pressure. Upon theaddition of excess 2-B alcohol, there was obtained a precipitate of amixture of approximately equal parts of gamma-fiuoro-alpha-aminobutyricacid and gamma-hydroxy-alpha-aminobutyric acid. The fluoro acid can beseparated from the hydroxy acid by fractional crystallization frommixtures of ethanol and water.

EXAMPLE 11 Part A.Preparation of ethyl acetamido(3-fluoropropyl)malonate To a solution of 23 parts of sodium in about 800 parts ofabsolute ethyl alcohol was aided 21? parts of ethyl acetamidomalonateand 14? parts of 1-bromo-3-fluoropropane (Hofimann, loo cit.) Theresulting mixture was heated at the reflux for 15 hours and the whiteprecipitate of sodium bromide removed by filtration. Upon evapora tionof the filtrate, a white crystalline mass was obtained. After washingwith water and recrystallization from 2-B alcohol, there was thusobtained 174- parts (63% yield) of ethylacetamido(3-fluoropropyl)malonate in 3 crops as white crystals, meltingat 7677 C.

Found: F, 6.7 N, 5.00% 7.0%; 5.03%

Part B.Preparation of delta-fluoronortaline A mixture of 140 parts ofthe above ethyl acetamido(3-fluoropropyl)malonate, 325 parts of 48%hydrofluoric acid, and parts of water were charged into apressure-resistant vessel, the vessel then sealed, and the contentsheated for 5 hours at 12 C. At the end of this reaction period, thereactor was cooled in an icewater bath, opened, and solid calciumhydroxide added in portions to bring the pH of the reaction mixture to3.5 (about 300 parts required). The resulting precipitate or" calciumfluoride was removed by filtration and washed with water. The aqueousfiltrate was then evaporated to dryness under reduced pressure, and thesolid residue thereby obtained extracted with excess 2B alcohol. Uponrecrystallization of the alcohol insoluble residue from an ethanol/watermixture, there was obtained 18.5 parts (27% yield) ofdelta-fluoronorvaline as resplendent plates melting at C.

Anal.Calcd fOl' C5H10NO2F: F, 14.1%; N, 10.4% Found: F, 14.0%; N, 10.2%14.2%; 10.1%

Aqueous solutions of delta-fluoronorvaline at concentrations of 0.1 and0.02% in a regular greenhouse preventive fungicide test were sprayed onbean plants and, 24 hours after spraying the plants, were inoculatedwith bean rust (Uromyces appendiculatus). Control plants which were notsprayed were treated similarly under the same conditions. Seven daysafter inoculation the sprayed plants exhibited no rust whatever whereasthe control plants were heavily covered with rust pustules. The sprayedplants were reinoculated with bean rust and after eight additional daysthe plants sprayed with the 0.1% deltafluoronorvaline solution exhibitedno rust whatever on either the primary, or new, secondary leaves. Theplants sprayed with the less concentrated solution exhibited a smallamount of rust on the new, secondary leaves, but none on the primaryleaves. These results show the activity of this material as a systemicfungicide and, as applied here in a foliar spray, demonstrate that it istranslocated to other parts of the plant and protects new growth. lheseresults also suggest that the delta-fluoronorvaline acts as a curativefungicide killing established infections at least in the earlier stages.

The same plants were again reinoculated and after six additional daysthe plants sprayed with the less concentrated solution exhibited somerust on the older, secondary leaves, but less than half the amountdeveloping on the control plants and none on the younger, secondaryleaves. The plants sprayed with the more concentrated solution exhibitedonly about 25% (based on the controls) disease on the older secondaryleaves and none on the younger secondary leaves. These results show thatdelta-fluoronorvaline, as applied here in a foliar spray, continues tomove, i. e., is translocated in the plant to the youngerattestsfirti'dfis provides protection to the new rbwth. It is to benoted that this protection as described above is effective over a periodof 21 days, and presumably longer, even inthe face of three inoculationswith the disease. The control plants were heavny infected during and atthe end or the test. p

To demonstrate the efficacy of delta=fluoronor= valine as a curativefungicide, Pinto variety bean prams were inoculated with a sporesuspension of bean rust and the plants placed in a humidity chamber topermit infection to develop; Tweri ty rcur and 48 hours afterinoculation, duplicate sets or the plants were sprayed with an aqueous0.2% solution of delta fluoronorvaline. Nine days" after inoculation thetreated plants in both sets exhibited no rust whatever; whereas, bothsets of uns'praye'd, inoculated controls were heavily infected. Theseresults demonstrated that deltafluoronorvaline functions as a curas tivefungicide, In contrast, under like conditions, plants sprayed andinoculated with 0.2% aqueous solutions of the closely related compoundDL- iio'rvaline exhibited 89% and 88% infection based on the controlplants, rated as 100%. To further demonstrate the systemic action ofdelta-fluoro fiorvaline, the above described sets of plants wereieifiocula'ted with bean rust. After seven addi tipnal days thedelta-fluoronorvaline sprayed plants exhibited a very small amount ofrust on the primary leaves, but none on the secondary leaves, with nonoticeable plant injury. In contrast, the control plants were heavilyinfected.

Further demonstrations of the outstanding effidienoy ofdelta-fiuoronorvaline as a curative fungicide were obtained bysprayingsimilar sets of Pinto bean test plants with aqueous 0.1% solutions ofthe compound, 24 and 48 hours after inoculations with bean rust.Complete control of the disease was obtained in both sets. Thisperformance, in so far as known published data reveals, is unique amongknown fungicides.

In a regular screening test for aphicidal activitydelta-'fluoroiiorvaline was found to be a highly effective material forcontrolling these insects. In particular, when petioles of excisednasturtiuin leaves infected with aphids were immersed in aqueus'solutions of delta-fluoronorvaline even at concentrations as low as 0.01to 0.05% by weight, the compound was translocated rapidly through thevascular system of the leaf and led to essentially a complete kill ofthe aphids sucking the plantsap. The high systemic insecticidal activityof delta-fluoronorvaline is also demonstrated in aqueous sprays appliedto the intact leaf surface or through the roots. Thus,deltafluoronorvaline is an extremely effective systemic insecticide whensprayed on the plants or applied to the soil in which the plant isgrowing. In similar tests closely related DL-norvaline was ineffective.

The copper salt of delta-fluoronorvaline is also an effective fungicide.It is nearly insoluble in water and may be applied in aqueous suspensionor as a dust.

EXAMPLE III Part A.'Prepamtioit of ethyl acetamido (4-fluorobutyl)-malonate To a solution of 18.6 parts of sodium, dissolved in about 630parts of absolute ethyl alcohol, was added 175 parts of ethylacetamidomalonate and 128 parts of l-bromo-4-fluorobutane (Hoffmann,lo'c. cit.). The resulting mixture was heated at the reflux for hoursand the precipitated 6. sodiumbromide removed by filtration. After removing the alcohol from the resulting filtrate by: evaporation',therewas obtained a crude syrup of 210 parts of theory) of ethylacetamidol-fluorobutyl) malonate.

Part B.'Prepa'ration of epsilon fluoronorleucine' A reactor was chargedwith parts of the above crude ethyl acetam'ido( 4-'fluorobutyl)mal onateand 360 parts of 48% hydrofluoric acid and the reaction mixture heatedon a steam'bath for 15' hours. The resulting solution was then cooled toroom temperature, diluted with 1500 parts of water, and neutralized topH 6 by the addition of solid calcium hydroxide (about 340-350 partsrequired). The precipitated calcium fluoride was removed by filtration,washed with water, and the aqueous filtrate then evaporated to dryriess.The crude solid epsilon-fluoronorleucine thus obtained was dissolved inexcess water and heated with 70 parts" of basic copper carbonate toconvert it to its sparingly soluble copper salt, which was removed byfiltration, washed with water, and subsequently decomposed in aqueoussuspension with gaseous hydrogen sulfide. The precipitated coppersulfide was then removed by filtration and the aqueous filtrateevaporated to dryness. Upon recrystallization of the solid residuethereby obtained from ethanol/water mixture, there was obtained 50.6parts (55% or theory) of epsilon-fluoronorleucme as white crystals,melting at 144 C.-

AndL-Calcd for C6H12NO2F F, 12.7% N, 9.39% Found: F, 12.1%; N ,9.l4%

EXAMPLE IV Part A.Prepa-rat2on of 5-methyZ5-trifluoromethylhydantoin Toa solution of 11.2 parts of LLL-trifluoroacetone in an ice c old mixtureof about 24 parts of 2-3 alcohol and ailpa'rts of water in a-reactionflask, fitted with a reflux condenser (jacket temperature, 7 C.), wasadded 23 parts of solid am- 111011111111 carbonate and a solution of 5.6parts of sodium cyanide in 15 parts of water. The rea action solutionwas heated at 50-66" C'. for 1.5 hours and the solvents removed byevaporation under reduced pressure. The resulting residue was takenup inwater and the solution neutralized to pH 4 with aqueous 10% hydrochloricacid in a hood to avoid possible fumes of HCN. The solution therebyobtained was then extracted three times with excess diethyl ether. .Uponevaporation of the ether extracts to dryness, there was obtained 6.1parts of crude, crystalline product from which by recrystallization fromwater, there was obtained 1.2 parts (23% yield) of5-methyl-5-trifluoromethylhydantoin as white crystals, melting at 137 C.

AnaZ.-Calcd for CsHsNzOzFst F, 313%; N, 15.4% Found! F, 30.5%; N, 15.4%29.9%; 15.3%

Pdrt B.-Preparation of alpha-amino-beta, beta,beta-trifluoroisobutyrz'c'acid A mixture of 10 parts of the above5-metliyl 5-trifluoromethylhydantoin and about 38 parts of 60% aqueoussulfuric acid were heated at the reflux for 48 hours. The unreac'tedsulfuric acid was then removed by treatment with a hot aqueous "10%solution of barium hydroxide until no further precipitate formed. Theprecipitated barium sulfate was removed by filtration and the filtrateconcentrated to small volume. Excess basic copper carbonate (8 parts)was then added to the concentrate and the resulting mixture heated toform the sparingly soluble copper salt ofalpha-amino-beta,beta,beta-trifluoroisobutyric acid. The reactionmixture was then cooled and the insoluble copper salt removed byfiltration, washed with cold water, and then suspended in water, andfinally decomposed with gaseous hydrogen sulfide. The precipitatedcopper sulfide was removed by filtration and the aqueous filtrateevaporated to dryness to yield 6.6 parts of crude, solid product. Uponrecrystallization from 2-B alcohol, there was obtained 5.0 parts (58%yield) of pure alpha-aminobeta,beta,beta-trifluoroisobutyric acid aswhite crystals which sublime rapidly at 250300 C. Anal.-Calcd forC4H6NO2F31 F, 36.3%; N, 8.92% Found: F, 35.5%; N, 8.87% 35.0%; 8.83%

EXAMPLE V Part A.-Preparation of 5-(2,2,3,3-tetrafluoro-1-methylcyclobut'yl) hydantoin To a solution of 85 parts ofl-formyl-l-methyl- 2,2,3,3-tetrafiuorocyclobutane (see Coii'man,Barrick, Cramer and Raasch, J. Am. Chem. Soc. 71, 494 (1949)) in about118 parts of 2-B alcohol and 100 parts of water, was added 114 parts ofsolid ammonium carbonate followed by a solution of 28 parts of sodiumcyanide in 75 parts of water over a period of minutes. The reactionmixture was stirred at 56-61 C. for 2 hours and then evaporated on asteam bath to semi-dryness. The solid obtained was neutralized to pH 4with aqueous 10% hydrochloric acid in a hood and the white crystallineproduct removed by filtration and washed with water. Uponrecrystallization of the product from 2-B alcohol, there was obtained 59parts (49% yield) of 5-(2,2,3,3-tetrafiuoro-l-methylcyclobutyl)hydantoinas white crystals, melting at 241-243 C.

Anal.Calcd for CaI-IsNzO2F4: N, 11.7%. Found: N, 11.1%.

Part B.Preparation of aZpha-amino-2,2,3,3-

tetrafluoro-I-methylcyclobutaneacetic acid A mixture of parts of theabove 5-(2,2,3,3 tetrafluoro 1 methylcyclobutyl)hydantoin and 200 partsof aqueous 60% sulfuric acid was heated at the reflux for 64 hours. Theresulting solution was then diluted to a total volume corresponding to700 parts of water, the solid removed by filtration, and the pH of thefiltrate adjusted to 6.4 with aqueous ammonium hydroxide. On standing,28 parts of alpha-amino-2,2,3,3-tetrailuorol-methylcyclobutaneaceticacid crystallized out and an additional 18.5 parts of the product wasobtained on concentrating the aqueous filtrate. The total yield (38.5parts) represents 68% of theory.

Anal.--Calcd for C7H9NO2F4:

F, 35.3%; C, 39.1%; H, 4.22% Found: F, 34.9%; C, 38.9%; H, 4.45% 34.7%;38.5%; 4.24%

It will be understood the above examples are merely illustrative andthat the invention broadly comprises that class or" aminocarboxylicacids wherein a carbon alpha to a carboxyl carries an amino group andeither a fluorosubstituted aliphatic or cycloaliphatic radical.

Preparation of compounds of the present invention other than those inthe examples can be effected by the Strecker type synthesis, or,preferiii ably, the Bucherer et a1. modification thereof. Thus,delta,delta,delta-trifiuoronorvaline can be prepared fromgamma,gamma,gammatrifluor0- butyraldehyde;delta,delta,delta-trifiuoro-alpha- (3,3,3-trifluoropropyl)norvaline from1,1,1,7,7,7- hexafiuoro 4 heptanone; delta,delta,delta-trifluoro gammatrifluoromethylnorvaline from 1,1,l,5,5,5-hexafluoro2-pentanone;alpha-aminohexafluoroisobutyric acid from hexafiuoroacetone; andalpha-amino-beta,beta-difluoroisobutyric acid from 1,1-difluoroacetone.The condensation of a fiuorosubstituted aliphatic or cycloaliphaticbromide or chloride with the sodio derivative of the above mentionedtype esters, followed by hydrolysis, can be used to preparedelta,delta-difluoronorvaline from l-bromo-3,3- difiuoropropane;gamma-fiuoronorvaline from 1- bromo-2 fluoropropane; alpha-amino-gamma,gamma-difiuorobutyric acid from l-bromo-2,2- difluoroethane; andepsilon,epsilon,epsilon-trifluoronorleucine froml-bromo-4,4,4-trifluorobutane. The aldehyde condensation with hydantoinroute, for example, can be used to prepare epsilon,epsi1on,epsilontrifluoronorleucine from gamma,gamma,garmna-trifluorobutyraldehyde.

As mentioned previously, the preferred fluorosubstituted aliphaticalpha-aminocarboxylic acids of this invention, including the metal, e.g., the alkali metal and alkaline metal earth, salts through thecarboxylic acid group and the hydrohalic acid salts through the aminogroup, are outstanding because of their particularly good physiologicalactivity. These compounds are useful as curative fungicides, systemicaphicides,

rodent poisons, and the like. These compounds exhibit the important, andthus far not completely understood, property of being translocated inplants; for instance, when applied externally to plant systems, i. e.,as a soil spray or a soil additive in concentrations as low as 0.02%,the compounds are absorbed into the plant system, translocatedthroughout to the stems and leaf systems and render the thus treatedplants resistant to fungi and aphids, without causing any noticeableplant injury.

Such properties obviously are of extreme importance since they permiteasy pretreatment of soil prior to planting or seeding and render theplants grown in such soils resistant to fungi and aphids, and thusobviate the necessity of constant spraying of the growing plant toprevent such infections. This latter traditional route for protectinggrowing plants against fungi and aphids is obviously more cumbersome,more time consuming, and less eiiicient. Using the traditional plantspray technique, constant spraying on a regular schedule must bepracticed. Using the preferred amino acids of this invention aspre-treating agents for the soil leads to the production of plants,resistant to these invading organisms with no further treatment.

The fluorosubstituted aliphatic and cycloaliphatic aminocarboxylic acidsof this invention are also useful as intermediates in the preparation oflow molecular weight synthetic polypeptides which again are of utilityas physiologically active compounds and also in the preparation of highmolecular weight filmand fiberforming amino acid polymers, for instance,as obtained through the N-carboanhydride route explained in greaterdetail in U. S. Patents 2,534,283; 2,572,843; 2,572,844; and 2,592,447.

As many apparently widely different embodiments of this invention may bemade without 9 departing from the spirit and scope thereof, it is to beunderstood that the invention is not limited to the specific embodimentsthereof except as defined in the appended claims.

The invention claimed is:

1. An aminocarboxylic acid wherein a carbon alpha to a carboxyl carriesan amino group and a radical from the group consisting of fiuoroalkyland fluorocycloalkyl radicals.

2. An alpha-monoaminomonocarboxylic acid wherein the carbon alpha to thecarboxyl carries a fiuoroalkyl radical.

3. An alpha-monoaminomonocarboxylic acid as set forth in claim 2 inwhich the alpha-amino group is primary.

4. An alpha-monoaminomonocarboxylic acid wherein the carbon alpha to thecarboxyl carries a single hydrogen and a fluorosubstituted, saturatedstraight chain alkyl radical in which the fluorine atoms are located onodd numbered carhome of the carbon chain.

5. An alpha-monoaminomonocarboxylic acid as set forth in claim 4 inwhich the carbon chain contains an odd number of carbons.

6. An alpha-monoaminomonocarboxylic acid as set forth in claim 5, saidacid having a single fluorine substituent and that on the terminalcarbon of the carbon chain of said acid and the alpha-amino group beingprimary.

'7. An aminocarboxylic acid having the formula 10 wherein R is afluorosubstituted. saturated straight chain alkyl radical in which thefluorine atoms are located on odd numbered carbons of the carbon chain.

8. An aminocarboxylic acid as set forth in claim 7 wherein R. is amonofluorosubstituted, saturated straight chain alkyl radical containingan odd number of carbons but no more than 5, the terminal carboncarrying the single fluorine atom.

9. An alpha-monoaminomonocarboxylic acid wherein the carbon alpha to thecarboxyl carries a fiuorocycloalkyl radical.

10. An alpha-monoaminomonocarboxy1ic acid as set forth in claim 11 inwhich the alphaamino group is primary.

JOHN FRANK LONTZ. MAYNARD STANLEY RAASCH.

References Cited in the flle of this patent UNITED STATES PATENTS NameDate Barrick et a1. May 11, 1948 OTHER REFERENCES Number

1. AN AMINOCARBOXYLIC ACID WHEREIN A CARBON ALPHA TO A CARBOXYL CARRIESAN AMINO GROUP AND A RADICAL FROM THE GROUP CONSISTING OF FLUOROALKYLAND FLUOROCYCLOALKYL RADICALS.